The following paragraphs are provided by way of background to the present disclosure. They are not however an admission that anything discussed therein is prior art or part of the knowledge of persons skilled in the art.
The biochemical pathways of living organisms are commonly classified as being either part of primary metabolism or part of secondary metabolism. Pathways that are part of a living cell's primary metabolism are involved in catabolism for energy production or in anabolism for building block production for the cell. On the other hand, secondary metabolites are produced by living cells and may lack any obvious anabolic or catabolic function. It has however long been recognized that many secondary metabolites are useful in many respects, including for example as therapeutic agents.
The secondary metabolite (S)-norcoclaurine is produced by opium poppy (Papaver somniferum) and by other members mainly of the Papaveraceae, Ranunculaceae, Berberidaceae and Menisperluaceae families of plants. (S)-norlaudansoline has not been found in nature, but is structurally similar to (S)-norcoclaurine and can be synthesized using the same suite of natural enzymes. (S)-norcoclaurine, (S)-norlaudanosoline, and synthesis intermediates thereof may be used as a raw material to manufacture alkaloid compounds that are useful as medicinal compounds, as well as recreational drugs or stimulants. Examples of such alkaloid compounds include the narcotic analgesics codeine and morphine, the antimicrobial agents sanguinerine and berberine, the muscle relaxants papaverine and (+)-tubocurarine, and the cough suppressant and potential anticancer drug noscapine.
Currently (S)-norcoclaurine and certain (S)-norcoclaurine synthesis intermediates may be harvested from natural sources, such as opium poppy. Alternatively these compounds may be prepared synthetically. (S)-norlaudanosoline may be prepared synthetically. However, the existing manufacturing methods for (S)-norcoclaurine, (S)-norlaudanosoline, and synthesis intermediates thereof suffer from low yields of (S)-norcoclaurine, (S)-norlaudanosoline, and synthesis intermediates and/or are expensive. In addition, synthetic manufacturing methods commonly lead to high volumes of waste materials such as organic solvents and metal catalysts. There exists therefore in the art a need for improved methods for the synthesis of (S)-norcoclaurine, (S)-norlaudanosoline, and synthesis intermediates thereof.